The pathophysiology of functional (psychogenic) movement disorders (FMD) is very poorly understood. These disorders are common in the population, diagnosis is difficult and treatment typically ineffective. We are studying the mechanisms underlying these disorders using cognitive tasks, neurophysiological testing, psychiatric measures, and functional imaging. One functional imaging study was an fMRI investigation of patients with tremor, and results showed abnormally reduced activation in the temporoparietal junction region. We have initiated similar studies in patients with functional myoclonus. We are also looking for abnormal activations related to tasks that probe functions such as emotional expression and movement inhibition, and have already shown abnormal activation in the amygdala. In the last year, we have done studies of fear conditioning, which is mediated by the amygdala. We have also investigated these patients for their sense of agency during fMRI studies, similar to the way we have studied normal subjects. In a large on-going study, with psychiatric help, we are exploring the biopsychosocial underpinnings of functional movement disorders. This large study is now getting to the point where we can begin in mine the large database, and we are beginning with neuroimaging studies. The origin of tics is generally unknown, and we have been approaching physiology in several ways. Tourette syndrome patients report premonitory urge and other sensory abnormalities associated with the presence of tics. We have been studying tic genesis with functional neuroimaging and EEG, and have pursued a series of studies looking at the physiology of the sensory urge. We will also be seeing if we can influence urge with brain stimulation. Tics may come about because of decreased inhibitory mechanisms in brain, and we have found that there is abnormal distribution of GABA receptors in the brain with neuroimaging techniques. On the basis of the idea that tics may represent bad habits, we are looking at the speed of making and breaking different types of behavioral choices. For many years, we have been collecting families with essential tremor looking for possible genetic abnormalities, and in the past year have identified a possible mutated gene in one of our families.. This work is being pursued with additional sequencing in conjunction with Drs. Camilo Toro, Lev Goldfarb, David Goldman and Andrew Singleton. While it is known that many patients with essential tremor respond to ethanol, it is not clear how many and what the physiology of the response is. We are investigating this including TMS measures of cortical excitability.